Aim 1) Serum biomarkers of neuronal (neuron specific enolase and ubiquitin carboxy-terminal hydrolase-L1) and glial injury (S100b and glial fibrillary acidic protein) Aim 2) Regional (occipital-parietal cortex, basal ganglia, and thalamus) brain MRI (T1/T2 and diffusion-weighted imaging) and magnetic resonance spectroscopy (MRS) biomarkers of neuronal injury (N-acetyl-aspartate) and energy failure (lactate) Aim 3 will model the combination of strong serum and imaging biomarkers of brain injury with clinical variables. We will assess serum biomarkers of brain mitochondrial injury with potential for novel therapeutic targets (cardiolipin and oxidized cardiolipin) in an exploratory aim. This proposed research is innovative, because a combined panel of serum and imaging biomarkers with clinical variables to accurately classify outcome after pediatric CA will be prospectively developed and optimized. These proposed aims leverage recent pilot successes and should generate accurate and reliable models of biomarkers that markedly improve post-resuscitation clinical care in children after CA. Furthermore, these results are expected to have a positive impact in advancing neurocritical care for these children, with forthcoming development of a serum biomarker point of care test and biomarker panels that will accurately classify risk of unfavorable outcome for clinicians and researchers needing to stratify by severity of injury, to monitor response to therapy, and ultimately to assist in their rehabilitation and recovery.